Antiviral Research 63 (2004) 123–131 Hepatitis B and C viral load changes following initiation of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection David M. Asmuth a, , Michael P. Busch b,c , Megan E. Laycock b,c , Beth A. Mohr d , Leslie A. Kalish d , Charles M. van der Horst e , Viral Activation Transfusion Study (VATS) Group 1 a Department of Internal Medicine, University of California—Davis Medical Center, Sacramento, CA, USA b Blood Centers of the Pacific, San Francisco, CA, USA c Blood Systems, Inc., Scottsdale, AZ, USA d New England Research Institutes, Watertown, MA, USA e Department of Medicine, University of North Carolina Medical School, Chapel Hill, NC, USA Received 27 August 2003; accepted 29 March 2004 Abstract Chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) is frequently present in patients seropositive for human immunodeficiency virus (HIV) because of shared routes of transmission. With the advent of highly active antiretroviral therapy (HAART) regimens capable of controlling HIV replication and dramatically prolonging the survival of HIV-infected patients, the impact of co-morbid infections such as HBV and HCV has come into focus. Several studies have monitored HBV or HCV viral loads following initiation of HAART, with disparate results. The effects of HAART on hepatitis B and C plasma viral loads (n = 9 and 32, respectively) and on liver enzyme levels were studied in a large cohort of prospectively studied subjects with advanced stage HIV disease. Comparing the mean pre- and post-HAART levels, there was an estimated increase of (a) 1.40log 10 from 4.83 to 6.24 log 10 for HBV plasma viral load (P = 0.07), (b) 0.74 log 10 from 6.38 to 7.12 log 10 for HCV plasma viral load (P = 0.001), and (c) 19.4 U/L from 37.4 to 56.8 U/L for serum alanine aminotransferase (P< 0.001). While the number of subjects co-infected with HIV and HBV was limited, these data collected in a population of advanced stage HIV-infected patients raises questions regarding the interactions of these viruses with each other and the host immune system and has implications regarding the order in which antiviral therapies are initiated. © 2004 Elsevier B.V. All rights reserved. Keywords: Antiretroviral therapy; Hepatitis B; Hepatitis C; Human immunodeficiency virus; Viral load 1. Introduction Chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) is frequently present in patients seropositive for human immunodeficiency virus (HIV) be- cause of shared routes of transmission. An estimated 10 and 30% of HIV-infected persons are co-infected with HBV or HCV, respectively (Perrillo et al., 1986; Bodsworth et al., 1991; Poles and Dieterich, 2000; Sulkowski et al., 2000a; Tedaldi et al., 2003b). Although the effect of HBV and HCV co-infection on HIV disease progression is uncertain, it is This work was supported in part by NHLBI (see Appendix A), as well as by reagents and testing by Roche Molecular Systems. Corresponding author. Tel.: +1-916-734-8695; fax: +1-916-734-7766. E-mail address: dasmuth@ucdavis.edu (D.M. Asmuth). 1 VATS study group membership is detailed in Appendix A. believed that HBV does not substantially alter HIV disease (Koblin et al., 1992; Gilson et al., 1997). Whereas some investigators have observed that HCV co-infection may be associated with a more rapid rate of HIV disease progres- sion (Bonacini and Puoti, 2000; Greub et al., 2000; Daar et al., 2001) compared to HCV seronegative HIV positive patients, others have not observed significant differences be- tween the two groups (Sulkowski et al., 2002a). Conversely, HIV co-infection reduces seroconversion and control of HBV infection (Gilson et al., 1997; Rodriguez-Mendez et al., 2000; Dore and Cooper, 2001; Martinez, 2001) and is associated with higher HCV viral loads and progression to cirrhosis (Eyster et al., 1994; Rockstroh et al., 1996; Martinez, 2001; Puoti et al., 2001; Sulkowski et al., 2002a) compared to HIV seronegative patients with the respective viral hepatitis. With the advent of highly active antiretro- viral therapy (HAART) regimens capable of controlling 0166-3542/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.antiviral.2004.03.006